Trial Outcomes & Findings for Radiation Therapy and Capecitabine With or Without Curcumin Before Surgery in Treating Patients With Rectal Cancer (NCT NCT00745134)
NCT ID: NCT00745134
Last Updated: 2023-09-28
Results Overview
Compared the rate of pCR between treatment arms with Fisher's exact test.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
22 participants
Primary outcome timeframe
At time of surgery
Results posted on
2023-09-28
Participant Flow
Participant milestones
| Measure |
Arm I (Curcumin)
Participants received CRT \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
Participants underwent radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
7
|
|
Overall Study
COMPLETED
|
15
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Arm I (Curcumin)
n=15 Participants
Participants received CRT \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
n=7 Participants
Participants underwent radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69 years
n=15 Participants
|
50 years
n=7 Participants
|
60 years
n=22 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=15 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=22 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=15 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=22 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
15 participants
n=15 Participants
|
7 participants
n=7 Participants
|
22 participants
n=22 Participants
|
|
Clinical T (Tumor) Stage
T2
|
3 Participants
n=15 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=22 Participants
|
|
Clinical T (Tumor) Stage
T3
|
11 Participants
n=15 Participants
|
6 Participants
n=7 Participants
|
17 Participants
n=22 Participants
|
|
Clinical T (Tumor) Stage
T4
|
1 Participants
n=15 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=22 Participants
|
|
Clinical N (Nodal) Stage
N0
|
3 Participants
n=15 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=22 Participants
|
|
Clinical N (Nodal) Stage
N1
|
11 Participants
n=15 Participants
|
4 Participants
n=7 Participants
|
15 Participants
n=22 Participants
|
|
Clinical N (Nodal) Stage
N2
|
1 Participants
n=15 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=22 Participants
|
|
Tumor Size
|
4 cm
n=15 Participants
|
5 cm
n=7 Participants
|
4.5 cm
n=22 Participants
|
|
Distance from anal verge
|
3 cm
n=15 Participants
|
6.5 cm
n=7 Participants
|
4 cm
n=22 Participants
|
|
Tumor circumference
|
50 cm
n=15 Participants
|
55 cm
n=7 Participants
|
50 cm
n=22 Participants
|
|
Pretreatment Carcinoembryonic Antigen (CEA)
|
1.3 ng/mL
n=15 Participants
|
2.4 ng/mL
n=7 Participants
|
1.6 ng/mL
n=22 Participants
|
|
Number of Participants with Tumor differentiation
Well Differentiated
|
0 Participants
n=15 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=22 Participants
|
|
Number of Participants with Tumor differentiation
Moderately Differentiated
|
15 Participants
n=15 Participants
|
7 Participants
n=7 Participants
|
22 Participants
n=22 Participants
|
|
Number of Participants with Tumor differentiation
Poorly Differentiated
|
0 Participants
n=15 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=22 Participants
|
PRIMARY outcome
Timeframe: At time of surgeryCompared the rate of pCR between treatment arms with Fisher's exact test.
Outcome measures
| Measure |
Arm I (Curcumin)
n=15 Participants
Participants received chemoradiation therapy (CRT) \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
n=7 Participants
Participants underwent radiation therapy and receive capecitabine as in Arm I. Participants received placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Number of Participants With Pathologic Complete Response (pCR) Rate
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Baseline to 11.5 weeksPopulation: Participants with analyzable tissue biopsies.
A logistic regression model with pCR as the dependent variable will be used to assess the association between pCR and NF-kB activity and treatment.
Outcome measures
| Measure |
Arm I (Curcumin)
n=12 Participants
Participants received chemoradiation therapy (CRT) \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
n=3 Participants
Participants underwent radiation therapy and receive capecitabine as in Arm I. Participants received placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Change in Curcumin Level in Tumor Tissue
|
33.7 ng/mg tissue
Interval 0.1 to 4765.7
|
0.0 ng/mg tissue
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: assessed 1 hr pre/post curcumin administration on one of the days during week 2 of radiation therapy (fractions 6-10)Plasma levels were assessed pre and post curcumin/placebo administration. During week 2 (after at least 5 fractions of radiation therapy) of chemoradiation therapy: 1. Optional endoscopic biopsy 2. Optional blood collection for pharmacology (1 hour before and 1 hour after intake of curcumin or placebo)
Outcome measures
| Measure |
Arm I (Curcumin)
n=15 Participants
Participants received chemoradiation therapy (CRT) \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
Participants underwent radiation therapy and receive capecitabine as in Arm I. Participants received placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Change in Curcumin Level in Serum
Serum curcumin concentrations before curcumin/placebo administration.
|
3.04 ng/mL
Interval 1.24 to 18.88
|
—
|
|
Change in Curcumin Level in Serum
Serum curcumin concentrations after curcumin/placebo administration.
|
3.32 ng/mL
Interval 0.84 to 5.36
|
—
|
SECONDARY outcome
Timeframe: Baseline to 11.5 weeksPopulation: One patient who did not undergo surgical resection was removed from analyses related to pathologic response outcomes.
tumor regression grade (1= pCR, 2= near pCR, 3= partial response, 4= no response, 5=progression).
Outcome measures
| Measure |
Arm I (Curcumin)
n=15 Participants
Participants received chemoradiation therapy (CRT) \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
n=6 Participants
Participants underwent radiation therapy and receive capecitabine as in Arm I. Participants received placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Tumor Regression Grade
Grade 1
|
1 Participants
|
2 Participants
|
|
Tumor Regression Grade
Grade 2
|
2 Participants
|
1 Participants
|
|
Tumor Regression Grade
Grade 3
|
4 Participants
|
1 Participants
|
|
Tumor Regression Grade
Grade 4
|
8 Participants
|
2 Participants
|
|
Tumor Regression Grade
Grade 5
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: One patient who did not undergo surgical resection was removed from analyses related to pathologic response outcomes.
OS was calculated from start of CRT to date of death, censored at last follow-up. Estimated with the Kaplan-Meier method.
Outcome measures
| Measure |
Arm I (Curcumin)
n=15 Participants
Participants received chemoradiation therapy (CRT) \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
n=6 Participants
Participants underwent radiation therapy and receive capecitabine as in Arm I. Participants received placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Overall Survival (OS)
|
85.7 percentage of participants
Interval 69.2 to 100.0
|
85.7 percentage of participants
Interval 63.3 to 100.0
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: One patient who did not undergo surgical resection was removed from analyses related to pathologic response outcomes.
PFS was calculated from start of CRT to date of disease progression or death, censored at last endoscopy/imaging evaluation.
Outcome measures
| Measure |
Arm I (Curcumin)
n=15 Participants
Participants received chemoradiation therapy (CRT) \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
n=6 Participants
Participants underwent radiation therapy and receive capecitabine as in Arm I. Participants received placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Progression Free Survival (PFS)
|
66.7 percentage of participants
Interval 46.6 to 95.3
|
71.4 percentage of participants
Interval 44.7 to 100.0
|
SECONDARY outcome
Timeframe: Baseline to 11.5 weeksPopulation: One patient who did not undergo surgical resection was removed from analyses related to pathologic response outcomes.
Tumor downstaging (DS) is defined as a decrease in the T stage of the primary tumor by at least 1.
Outcome measures
| Measure |
Arm I (Curcumin)
n=15 Participants
Participants received chemoradiation therapy (CRT) \[50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)\] followed by surgery. Curcumin (4 grams orally, twice daily)
|
Arm II (Placebo)
n=6 Participants
Participants underwent radiation therapy and receive capecitabine as in Arm I. Participants received placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Number of Participants With Tumor Downstaging
|
7 Participants
|
4 Participants
|
Adverse Events
Arm I (Curcumin)
Serious events: 1 serious events
Other events: 15 other events
Deaths: 6 deaths
Arm II (Placebo)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Arm I (Curcumin)
n=15 participants at risk
Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
|
Arm II (Placebo)
n=7 participants at risk
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Gastrointestinal disorders
Colitis
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
|
General disorders
Pain
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
Other adverse events
| Measure |
Arm I (Curcumin)
n=15 participants at risk
Patients undergo radiation therapy 5 days a week for a total of 28 fractions. Patients also receive capecitabine PO BID on the days of radiation therapy and curcumin PO BID in weeks 1-11.5.
|
Arm II (Placebo)
n=7 participants at risk
Patients undergo radiation therapy and receive capecitabine as in Arm I. Patients also receive placebo PO BID in weeks 1-11.5.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
0.00%
0/15 • 5 years
|
14.3%
1/7 • Number of events 1 • 5 years
|
|
Metabolism and nutrition disorders
Anorexia
|
53.3%
8/15 • Number of events 9 • 5 years
|
28.6%
2/7 • Number of events 2 • 5 years
|
|
Gastrointestinal disorders
Diarrhea
|
80.0%
12/15 • Number of events 13 • 5 years
|
42.9%
3/7 • Number of events 3 • 5 years
|
|
Nervous system disorders
Dizziness
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
|
Renal and urinary disorders
Dysuria
|
33.3%
5/15 • Number of events 6 • 5 years
|
0.00%
0/7 • 5 years
|
|
General disorders
Elevated liver function tests
|
0.00%
0/15 • 5 years
|
14.3%
1/7 • Number of events 1 • 5 years
|
|
General disorders
Fatigue
|
86.7%
13/15 • Number of events 13 • 5 years
|
85.7%
6/7 • Number of events 6 • 5 years
|
|
Skin and subcutaneous tissue disorders
Hand foot syndrome
|
26.7%
4/15 • Number of events 4 • 5 years
|
28.6%
2/7 • Number of events 2 • 5 years
|
|
Gastrointestinal disorders
Hemorrhoids
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
|
Vascular disorders
Hypotension
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
|
Psychiatric disorders
Insomnia
|
13.3%
2/15 • Number of events 3 • 5 years
|
0.00%
0/7 • 5 years
|
|
Infections and infestations
Infection
|
0.00%
0/15 • 5 years
|
14.3%
1/7 • Number of events 1 • 5 years
|
|
Gastrointestinal disorders
Nausea
|
66.7%
10/15 • Number of events 11 • 5 years
|
57.1%
4/7 • Number of events 4 • 5 years
|
|
Nervous system disorders
Neuropathy
|
0.00%
0/15 • 5 years
|
14.3%
1/7 • Number of events 1 • 5 years
|
|
General disorders
Pain
|
60.0%
9/15 • Number of events 10 • 5 years
|
71.4%
5/7 • Number of events 7 • 5 years
|
|
Injury, poisoning and procedural complications
Radiation dermatitis
|
80.0%
12/15 • Number of events 14 • 5 years
|
57.1%
4/7 • Number of events 6 • 5 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
|
Gastrointestinal disorders
Rectal bleeding
|
0.00%
0/15 • 5 years
|
14.3%
1/7 • Number of events 1 • 5 years
|
|
Reproductive system and breast disorders
Testicular swelling
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
|
Renal and urinary disorders
Urinary frequency
|
26.7%
4/15 • Number of events 4 • 5 years
|
28.6%
2/7 • Number of events 2 • 5 years
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
1/15 • Number of events 1 • 5 years
|
0.00%
0/7 • 5 years
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/15 • 5 years
|
14.3%
1/7 • Number of events 1 • 5 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place